AACR Virtual Annual Meeting 2020

E-Poster (LB-008): Patient-derived Organoids – Bringing the Patient in the Lab for Preclinical and Clinical Development

Preclinical disease models are essential for the development of novel therapies and help better understand the molecular processes. In recent years, a novel groundbreaking technology to generate patient specific in vitro cultures based on adult stem-cell organoids, has gained widespread interest for the development of new therapies and as a predictive diagnostic tool. ASC-derived organoids can be generated at high efficiency from both healthy and diseased tissue (resections as well as biopsies) including most carcinomas. These patient derived cultures can be expanded for prolonged periods of time while maintaining many properties of the tissue they were derived from. At HUB, we have created comprehensive ‘living biobanks’ from tumors of different origin like colon, lung, breast, pancreas and ovary. These biobanks have been characterized at the genetic and transcriptional level. These analyses have shown that our ‘living biobanks’ capture disease heterogeneity at the genetic and molecular level. Because organoids can be expanded long term, drug screening is feasible in these models. HUB has developed procedures for (high-throughput) compound screening in organoids including small molecules and biologics. In this setting, organoids have been used to identify novel targets, identify lead compounds and stratify potential responders based on their genetic or molecular profile. Recent advances in the field of immuno-oncology have revolutionized the treatment for cancer patients. Despite of the improvements and due to the complex and highly regulated nature of the immune system, treatment does not have a similar effect on all tumors. We have created a co-culture model of tumor derived organoids and immune cells. In these co-cultures, the cytotoxic effect of the immune cell on the tumor can be measured in a reproducible and quantitative manner. Currently we are expanding existing co-culture models to incorporate different immune cells and organoid tumor types. In addition, organoids can serve as a patient avatar in clinical development or diagnostics. In this setting, organoids could add a functional test for therapy response in a patient centered setting providing a unique tool for personalized medicine.

Presenter: Jasper Mullenders

Date: June 22

Time: 9 AM – 6 PM EDT

Session: LBPO.TB01 – Late-Breaking Research: Tumor Biology 1

E-Poster: Patient-derived Organoids

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